Three-fourths of the patients with breast and prostate cancer develop complications of bone metastasis. When cancer metastasizes to bone, it becomes almost incurable and creates considerable pain. Metastasizing cancer also deregulates bone remodeling, leading to bone fractures, hypercalcaemia, spinal cord and nerve compression syndromes.
The mineralized extracellular matrix and specific cell types in the bone microenvironment are controlled by local and systemic factors that create a special milieu to provide a fertile soil for many cancers in which to thrive, including metastasizing cancer from other distant organs and areas of the body. Cancer cells in bone secrete a vast array of proteins, many of which interact with resident cells in the bone marrow to induce the differentiation, recruitment and activation of osteoclasts and osteoblasts, inducing destructive osteolytic and/or bone forming osteoblastic lesions.
During the process of bone resorption, stored growth factors and ionized calcium are released from the mineralized bone matrix. These factors feedback to promote tumor cell growth and production of osteolytic and osteoblastic factors. This vicious cycle can support tumor growth in bone. The fertile environment of bone marrow can also serve as a storage space for dormant cancer cells, as these cancer cells can significantly resist localized radiation treatment and systemic chemotherapeutic attack, and later emerge as full-blown metastases in bone or other organs. Preferential delivery of therapeutic agents to the bone has potential to attach to these bone homing cancer cells and may significantly improve the clinical outcome.
There are several other bone disorders that would benefit from systems that can deliver therapeutics preferentially to bone. The common bone disorders such as osteoporosis, Paget's disease, multiple myeloma, myelo-proliferative disease besides skeletal metastasis of several epithelial cancers can have better treatment options if the therapeutic agents could be delivered in a site specific manner to bone.
In the case of designing and development of surgical implants used for applications such as joining of bones, research has been focused only on topological modification of implant surfaces for better integration of the implant into the tissue. Some preclinical studies have suggested coating of the implant surface with polymers or entrapping therapeutic molecules on the implant may have benefits. However, these strategies are limited by the harsh conditions and time-consuming procedures for coating the device, and offer little for practical applications.
There has been literally no practical solution when it comes to intraoperative modification procedure of the surgical implants for local drug delivery of therapeutics such as antibiotics, growth factors etc., for individualized patient treatment. There is a complete absence of any method that can provide flexibility of modifying surgical implants during an operation or in emergencies. A specific method or composition is needed for delivery of therapeutic molecules such as growth factors like bone morphogenic protein that can have drastic side effects on non-specific application and have short half-life, for example five minutes. Growth factors need to be at the site of implantation for days for effective bone formation at the implant surface. There is no effective strategy for local drug delivery at the surgical metal implant-bone tissue interface that can enhance osseointegration of implants in the tissue or that can actively promote the tissue growth at the implant surface.
It is therefore an object of the present invention to provide methods and compositions for targeting delivery of therapeutics for selective treatment of bone disorders.
It is another object of the present invention to provide methods and compositions for improving delivery of therapeutics at the tissue-implant interface.